{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T23:17:08Z","timestamp":1778541428877,"version":"3.51.4"},"reference-count":62,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T00:00:00Z","timestamp":1626393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPD1H0433"],"award-info":[{"award-number":["CMRPD1H0433"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Healthy Aging Research Center, Chang Gung University","award":["EMRPD1K0361"],"award-info":[{"award-number":["EMRPD1K0361"]}]},{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 107-2320-B-182 -019-MY3"],"award-info":[{"award-number":["MOST 107-2320-B-182 -019-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The precise neural mechanisms underlying the pathogenesis of depression are largely unknown, though stress-induced brain inflammation and serotonergic plasticity are thought to be centrally involved. Moreover, we previously demonstrated that neuropeptide FF receptor 2 (NPFFR2) overexpression provokes depressive-like behaviors in mice. Here, we assess whether NPFFR2 is involved in priming of depressive-like behaviors and downregulation of serotonergic 1A receptor (5HT1AR) after lipopolysaccharide (LPS) treatment. The forced swimming test (FST) and sucrose preference test (SPT) were used to quantify depressive-like phenotypes in wild-type (WT) and NPFFR2-knockout (KO) mice. A single dose of LPS (i.p. 1 mg\/kg) readily caused increases in toll-like receptor 4 and tumor necrosis factor-\u03b1 along with decreases in 5-HT1AR mRNA in the ventral hippocampus of WT mice. Furthermore, LPS treatment of WT mice increased immobility time in FST and decreased sucrose preference in SPT. In contrast, none of these effects were observed in NPFFR2-KO mice. While WT mice injected with lentiviral 5-HT1AR shRNA in the ventral hippocampus displayed an unaltered response after LPS challenge, LPS-challenged NPFFR2-KO mice displayed a profound decrease in sucrose preference when pretreated with 5-HT1AR shRNA. Taken together, these results suggest that NPFFR2 modulates LPS-induced depressive-like behavioral phenotypes by downregulating 5HT1AR in the ventral hippocampus.<\/jats:p>","DOI":"10.3390\/ijms22147611","type":"journal-article","created":{"date-parts":[[2021,7,16]],"date-time":"2021-07-16T10:52:58Z","timestamp":1626432778000},"page":"7611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Knockout of NPFFR2 Prevents LPS-Induced Depressive-Like Responses in Mice"],"prefix":"10.3390","volume":"22","author":[{"given":"Zachary","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Medicine, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7910-1223","authenticated-orcid":false,"given":"Ya-Tin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan 333, Taiwan"},{"name":"Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2996-5781","authenticated-orcid":false,"given":"Jin-Chung","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan 333, Taiwan"},{"name":"Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan"},{"name":"Neuroscience Research Center, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0140-6736(18)32279-7","article-title":"Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990\u20132017: A systematic analysis for the Global Burden of Disease Study 2017","volume":"392","author":"Disease","year":"2018","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"9927","DOI":"10.1038\/s41598-020-66672-9","article-title":"Sex differences in the genetic architecture of depression","volume":"10","author":"Kang","year":"2020","journal-title":"Sci. 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